LRRC23

Chr 12AR

leucine rich repeat containing 23

Also known as: LRPB7, SPGF92

NCBI Gene: 10233 ENSG00000010626 UniProt: Q53EV4 OMIM: 620708

The protein is essential for sperm motility and male fertility, specifically required for proper assembly of radial spoke structures in sperm flagella. Mutations cause spermatogenic failure 92, inherited in an autosomal recessive pattern. This gene shows low constraint against loss-of-function variants (LOEUF 1.218), consistent with its specialized role in male reproductive function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Involved in flagellated sperm motility and radial spoke assembly. Located in cytoplasm and sperm flagellum. Implicated in spermatogenic failure 92. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spermatogenic failure 92MIM #620848

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Spermatogenic failure 92; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.22

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.000

Z-score 0.87

OE 0.78 (0.51–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.25Z-score

OE missense 0.95 (0.84–1.07)

176 obs / 185.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.51–1.22)

0≤0.351.4

Missense OE?0.95 (0.84–1.07)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 14 / 18.0Missense obs/exp: 176 / 185.7Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in LRRC23?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

525 rare PASS variants

Rare truncating (LoF)

1 in 1,500

102 rare PASS variants

Rare synonymous (reference)

1 in 200

206 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LRRC23. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 2,100
South Asian	~43k	1 in 89	1 in 780
Remaining (unassigned)	~30k	1 in 120	1 in 1,000
European (Finnish)	~27k	1 in 610	≈ 1 in 27,000
Admixed American	~22k	1 in 71	1 in 2,300
African / African American	~21k	1 in 88	1 in 640
East Asian	~20k	1 in 180	1 in 800
Ashkenazi Jewish	~13k	1 in 790	1 in 410
Middle Eastern	~2,884	1 in 110	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓